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This paper provides an overview of the HEAT (Healthy Environments for AthleTes) project, which aims to understand the impact of environmental conditions on athlete health and performance during major sporting events such as long-distance running, cycling, and triathlons. In collaboration with the SAFER (Strategies to reduce Adverse medical events For the ExerciseR) initiative, the HEAT project carried out a field campaign at the 2022 Comrades Marathon in the KwaZulu-Natal province of South Africa. The measurement campaign deployed seven weather stations, seven PM2.5 monitors and one spore trap along the 90 km route to capture spatially representative measurements of complex micro-climates, allergenic aerospora, and particulate matter exposure. The results indicate that runners were exposed to moderate risk heat stress conditions. Novel findings from this initial campaign shows elevated and potentially harmful PM2.5 levels at spectator areas, possibly coinciding with small fire events around the race day festivities. Our findings show values PM2.5 levels over the WHO 24-h guidelines at all stations, while 2000 µg/m3 at two stations. However, the lack of an acute exposure standard means direct health impacts cannot be quantified in the context of a sport event. The HEAT project highlights important aspects of race day monitoring; regional scale climatology has an impact on the race day conditions, the microclimatic conditions (pollution and meteorology) are not necessarily captured by proximity instruments and direct environmental measurements are required to accurately capture conditions along the route. [ABSTRACT FROM AUTHOR]

The linear discriminant analysis (LDA) is a common technique used in machine learning and pattern recognition for dimensionality reduction problems. Here, the LDA is applied to detect faults‐scarps in high‐resolution bathymetric profiles in the Southern Pescadero Basin (SPB) in the Gulf of California. The LDA uses fault scarps and cuestas (sloping topography) identified by a geomorphologist in the neighboring Alarcón Rise (AR). These geometric representations are transformed into a parametric space by an idealized fault‐scarp degradation model. Through inversion, we extracted the product of the mass diffusion coefficient with time (τ), scarp height (u0), and goodness of fit of the model on the scarp profiles and cuestas (ε). The LDA transforms the parametric space τ, u0, ε by the Fisher's criterion into a 1D dimensional space that maximizes separability of classes. Then, the classification is performed by Bayes decision rule using the probability density functions (PDF) built from the 1D projected data for each class (fault‐scarps and cuestas). The implementation results in cross‐sectional profiles across the SPB show the ability to detect faults in the deepest part of the basin where the flat basin floor is interrupted by morphologically young fault‐scarp arrays. The LDA interpretation outperforms manual identification, particularly in faults scarps that are longer than ∼3 km, whereas shorter faults are challenging to discern from other linear features like channels. The model can extract information about the state of degradation of the scarps. This application allows the identification of fault generation episodes and resolves kinematic interactions between faults. Plain Language Summary: Geologists often have to investigate large amounts of data to identify new ideas about the processes that sculpt the Earth's surface. The data are usually not sufficiently classified, making structure identification a time‐consuming task. The effort is especially challenging in submarine environments, given their inaccessibility and difficulty in collecting direct observations. We present a semi‐automated method for detecting faults in high‐resolution gridded bathymetry data collected by an autonomous underwater vehicle. We use a machine‐learning technique to classify fault‐line scarps based on key geomorphological attributes measured from the scarp's erosion. The detection technique uses a brute‐force approach that systematically scans all the bathymetry data and searches for fault‐line scarps. The results of the proposed method detect fault‐scarps of different sizes and stages of degradation. Moreover, the method is robust to moderate noise (i.e., random topography and data collection artifacts) and correctly handles different fault dip angles. Tests show that both isolated and linkage fault configurations are detected and tracked reliably. The method can also get relative timing information of the faulting episodes. Getting all this information is valuable to understand the processes that shape submarine geomorphology. Key Points: Feature extraction using the solution of the diffusion equation for modeling fault‐scarp degradation by erosionLinear discriminant analysis technique is used for fault‐line scarp classification plus a windows search approach for detectionThe method provide information of spatial distribution, slip, timing and mode of growth of fault‐line scarps [ABSTRACT FROM AUTHOR]

Background: Very little is known about the risk that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection poses to cancer patients, many of whom are immune compromised causing them to be more susceptible to a host of infections. As a precautionary measure, many clinical studies halted enrollment during the initial surge of the global Novel Coronavirus Disease (COVID-19) pandemic. In this case report, we detail the successful treatment of a relapsed and refractory multiple myeloma (MM) patient treated with an anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy immediately following clinical recovery from COVID-19. Case presentation: The 57 year old Caucasian male patient had a 4-year history of MM and was considered penta-refractory upon presentation for CAR T cell therapy. He had a history of immunosuppression and received one dose of lymphodepleting chemotherapy (LDC) the day prior to COVID-19 diagnosis; this patient was able to mount a substantial immune response against the SARS-CoV-2 virus, and antiviral antibodies remain detectable 2 months after receiving anti-BCMA CAR T cell therapy. The recent SARS-CoV-2 infection in this patient did not exacerbate CAR T-associated cytokine release syndrome (CRS) and conversely the CAR T cell therapy did not result in COVID-19-related complications. One month after CAR T cell infusion, the patient was assessed to have an unconfirmed partial response per International Myeloma Working Group (IMWG) criteria. Conclusion: Our case adds important context around treatment choice for MM patients in the era of COVID-19 and whether CAR T therapy can be administered to patients who have recovered from COVID-19. As the COVID-19 global pandemic continues, the decision of whether to proceed with CAR T cell therapy will require extensive discussion weighing the potential risks and benefits of therapy. This case suggests that it is possible to successfully complete anti-BCMA CAR T cell therapy after recovery from COVID-19. CRB-402 study registered 6 September 2017 at clinicaltrials.gov (NCT03274219). [ABSTRACT FROM AUTHOR]

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A consistent device model to describe current-voltage characteristics of metal/insulator/metal systems is developed. In this model the insulator and the metal electrodes are described within the same theoretical framework using density of states distributions. This approach leads to differential equations for the electric field which have to be solved in a self-consistent manner by considering the continuity of the electric displacement and the electrochemical potential in the complete system. The model is capable of describing the current-voltage characteristics of the metal/insulator/metal system in forward and reverse biases for arbitrary values of the metal/insulator injection barriers. In the case of high injection barriers, approximations are provided offering a tool for comparison with experiments. Numerical calculations are performed exemplarily using a simplified model of an organic semiconductor. [ABSTRACT FROM AUTHOR]

The applicability of the Einstein relation considering diffusivity and mobility of charge carriers with respect to disordered systems has been a matter of serious discussion in recent years. Here the validity of the Einstein relation, using the generalized form, is checked for two specific density-of-states functions within a multiple trapping model and the mobility edge concept. It is shown that the classical Einstein relation is valid for almost all charge-carrier densities relevant for experimental purposes. It is demonstrated that this result is dependent on the charge-carrier mobility definition. [ABSTRACT FROM AUTHOR]

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Recent advancements in bioanalytical techniques have led to the development of novel and robust diagnostic approaches that hold promise for providing optimal patient treatment, guiding prevention programs and widening the scope of personalized medicine. However, these advanced diagnostic techniques are still complex, expensive and limited to centralized healthcare facilities or research laboratories. This significantly hinders the use of evidence-based diagnostics for resource-limited settings and the primary care, thus creating a gap between healthcare providers and patients, leaving these populations without access to precision and quality medicine. Smartphone-based imaging and sensing platforms are emerging as promising alternatives for bridging this gap and decentralizing diagnostic tests offering practical features such as portability, cost-effectiveness and connectivity. Moreover, towards simplifying and automating bioanalytical techniques, biosensors and lab-on-a-chip technologies have become essential to interface and integrate these assays, bringing together the high precision and sensitivity of diagnostic techniques with the connectivity and computational power of smartphones. Here, we provide an overview of the emerging field of clinical smartphone diagnostics and its contributing technologies, as well as their wide range of areas of application, which span from haematology to digital pathology and rapid infectious disease diagnostics. [ABSTRACT FROM AUTHOR]

Copyright of Herz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Kardiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nearly all classical inf-sup stable mixed finite element methods for the incompressible Stokes equations are not pressure-robust, i.e., the velocity error is dependent on the pressure. However, recent results show that pressure-robustness can be recovered by a nonstandard discretization of the right-hand side alone. This variational crime introduces a consistency error in the method which can be estimated in a straightforward manner provided that the exact velocity solution is sufficiently smooth. The purpose of this paper is to analyze the pressure-robust scheme with low regularity. The numerical analysis applies divergence-free H¹-conforming Stokes finite element methods as a theoretical tool. As an example, pressure-robust velocity and pressure a priori error estimates will be presented for the (first-order) nonconforming Crouzeix--Raviart element. A key feature in the analysis is the dependence of the errors on the Helmholtz projector of the right-hand side data, and not on the entire data term. Numerical examples illustrate the theoretical results. [ABSTRACT FROM AUTHOR]

Copyright of Der Kardiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Context: Risk alleles of the fat mass- and obesity-associated gene (FTO) are related not only to increased body mass index (BMI) values but also to mortality. It was speculated that cellular effects of the FTO gene affect most organs, especially their ability to maintain or regenerate proper function when afflicted by various diseases. FTO is highly expressed in the hypothalamus and also in the pituitary gland. The decrease in growth hormone (GH) secretion is known to cause a decrease in lean body mass in older subjects. Objective: We hypothesized an association of rs9926289 with insulin-like growth factor (IGF)-I. Design and Setting: Cross-sectional data from the Study of Health in Pomerania, a population-based study in the northeastern part of Germany, were used. Participants: For the final analyses, 3882 subjects aged 20-79 years were available. Main Outcome Measures: Continuous IGF-I, low IGF-I according to clinically meaningful age- and gender-specific reference values, and BMI were used as outcome measures. Results: Over all age groups, a statistically significant relationship between FTO and IGF-I was found. In subjects younger than 55 years of age, homozygous carriers of the FTO risk allele exhibited lower serum IGF-I levels adjusted for 5-year age groups, gender and IGF-I binding protein 3 levels (linear regression, coefficient±s.e. for FTO AA genotype:-8.6±2.8; P=0.002). Further adjustments for obesity and diabetes did not suspend this association (coefficient:-7.8; P=0.005). As expected, the FTO AA genotype effect on BMI was reduced from 0.76 to 0.62  kg  m(-2) by including IGF-I. No relationship between FTO and IGF-I levels was found in subjects aged 55 years or older (-2.7±2.4; P=0.260 for FTO AA genotype adjusted for age, gender and IGF-I binding protein 3 levels). Conclusion: We propose that the GH-IGF-I axis is a mediator for the relationship between FTO and BMI. [ABSTRACT FROM AUTHOR]

Study Objectives: The majority of thrombolysis studies require defined ST-segment elevations as an inclusion criterion for the diagnosis of acute myocardial infarction (AMI). However, depending on the occluded infarct vessel and the criteria applied, the ECG diagnosis of AMI can be difficult to establish. Accordingly, this study was performed to evaluate the sensitivity of ST-segment elevation of standard and extended ECG leads in a cohort of patients with angiographically confirmed diagnosis of AMI.Patients and Methods: In 418 patients (mean +/- SD age, 60 +/- 13 years) with AMI (pain onset, 4.8 +/- 3.0 h), coronary angiography with percutaneous transluminal coronary angioplasty/stenting of the culprit lesion was performed. The diagnosis of AMI was confirmed by emergency coronary angiography and laboratory analyses. ST-segment elevation (in two contiguous leads) of 1 mm in standard lead I through aVF and ST-segment elevations of 2 mm (or 1 mm, corresponding values presented in parentheses) in V(1) through V(6) were considered significant. In a subset of 102 AMI patients, additional right precordial leads V(3)R through V(6)R for evaluation of right ventricular infarction and additional chest leads V(7) through V(9) for evaluation of posterior infarction were recorded. ST-segment elevations of 1 mm in the right precordial leads and 1 mm or 0.5 mm in the posterior leads were considered significant.Results: Standard leads I through V(6) showed ST-segment elevation in 85% (96%) of patients with left anterior descending artery occlusion, in 46% (61%) of patients with left circumflex coronary artery (CX) occlusion, and in 85% (90%) of patients with right coronary artery occlusion. On consideration of additional ECG tracings in the subgroup of 102 patients (V(3)R through V(6)R and V(7) through V(9)), the respective numbers increased by 2 to 8% depending on different criteria for ST-segment elevation; in patients with CX occlusion, the increase amounted to 6 to 14%. There was a trend toward an extended infarct size (maximum creatine kinase [CK] values) with concomitant ST-segment elevation in additional ECG leads as assessed by maximum CK levels.Conclusions: The sensitivity of the ECG diagnosis of AMI is only marginally increased by extended precordial chest leads. There is a trend toward an extended infarct size in those patients with concomitant ST-segment elevation in additional ECG leads. [ABSTRACT FROM AUTHOR]

Copyright of Rechtsmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Dual antiplatelet therapy with aspirin and clopidogrel is the accepted standard for prevention of ischemic complications after percutaneous coronary intervention and has been shown to reduce cardiovascular events in patients with acute coronary syndromes (ACSs). There is substantial interindividual variability in antiplatelet response to clopidogrel. Various clinical studies have demonstrated that patients with high on-clopidogrel platelet reactivity incur an increased risk for ischemic events. In recent years, several clinical and demographic variables as well as multiple genetic factors contributing to the variability in antiplatelet response to clopidogrel have been identified. We discuss strategies based on platelet function testing or genotyping for improvement of antiplatelet effects of clopidogrel and thereby clinical outcome. [ABSTRACT FROM AUTHOR]

The austral westerlies strongly influence precipitation and ocean circulation in the southern temperate zone, with important consequences for cultures and ecosystems. Global climate models anticipate poleward retreat of the austral westerlies with future warming, but the available paleoclimate records that might test these models have been limited to South America and New Zealand, are not fully consistent with each other and may be complicated by influences from other climatic factors. Here we present the first highresolution diatom and sedimentological records from the winter rainfall region of South Africa, representing precipitation in the equatorward margin of the westerly wind belt during the last 1400 yr. Inferred rainfall was relatively high ∼1400-1200 cal yr BP, decreased until ∼950 cal yr BP, and rose notably through the Little Ice Age with pulses centred on ∼600, 530, 470, 330, 200, 90, and 20 cal yr BP. Synchronous fluctuations in Antarctic ice core chemistry strongly suggest that these variations were linked to changes in the westerlies. Equatorward drift of the westerlies during the wet periods may have influenced Atlantic meridional overturning circulation by restricting marine flow around the tip of Africa. Apparent inconsistencies among some aspects of records from South America, New Zealand and South Africa warn against the simplistic application of single records to the Southern Hemisphere as a whole. Nonetheless, these findings in general do support model projections of increasing aridity in the austral winter rainfall zones with future warming. [ABSTRACT FROM AUTHOR]

Copyright of Der Kardiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The austral westerlies strongly influence precipitation and ocean circulation in the southern temperate zone, with important consequences for cultures and ecosystems. Global climate models anticipate poleward contraction of the austral westerlies with future warming, but the available paleoclimate records that might test these models have been largely limited to South America, are not fully consistent with each other, and may be complicated by influences from other climatic factors. Here we present the first fineinterval diatom and sedimentological records from the winter rainfall region of South Africa, representing precipitation during the last 1400 yr. Inferred rainfall increased ∼1400-1200 cal yr BP and most notably during the Little Ice Age with pulses centered on ∼600, 530, 470, 330, 200, and 90 cal yr BP. Synchronous fluctuations in Antarctic ice core chemistry strongly suggest that these variations are linked to changes in the westerlies. Partial inconsistencies among South African and South American records warn against the simplistic application of local-scale histories to the Southern Hemisphere as a whole. Nonetheless, these findings in general do support model projections of increasing aridity in austral winter rainfall zones with future warming. [ABSTRACT FROM AUTHOR]

Context:Risk alleles of the fat mass- and obesity-associated gene (FTO) are related not only to increased body mass index (BMI) values but also to mortality. It was speculated that cellular effects of the FTO gene affect most organs, especially their ability to maintain or regenerate proper function when afflicted by various diseases. FTO is highly expressed in the hypothalamus and also in the pituitary gland. The decrease in growth hormone (GH) secretion is known to cause a decrease in lean body mass in older subjects.Objective:We hypothesized an association of rs9926289 with insulin-like growth factor (IGF)-I.Design and setting:Cross-sectional data from the Study of Health in Pomerania, a population-based study in the northeastern part of Germany, were used.Participants:For the final analyses, 3882 subjects aged 20-79 years were available.Main outcome measures:Continuous IGF-I, low IGF-I according to clinically meaningful age- and gender-specific reference values, and BMI were used as outcome measures.Results:Over all age groups, a statistically significant relationship between FTO and IGF-I was found. In subjects younger than 55 years of age, homozygous carriers of the FTO risk allele exhibited lower serum IGF-I levels adjusted for 5-year age groups, gender and IGF-I binding protein 3 levels (linear regression, coefficient±s.e. for FTO AA genotype:−8.6±2.8; P=0.002). Further adjustments for obesity and diabetes did not suspend this association (coefficient:-7.8; P=0.005). As expected, the FTO AA genotype effect on BMI was reduced from 0.76 to 0.62 kg m−2 by including IGF-I. No relationship between FTO and IGF-I levels was found in subjects aged 55 years or older (−2.7±2.4; P=0.260 for FTO AA genotype adjusted for age, gender and IGF-I binding protein 3 levels).Conclusion:We propose that the GH-IGF-I axis is a mediator for the relationship between FTO and BMI. [ABSTRACT FROM AUTHOR]

Great effort has been made to improve the knowledge about the behavior of granular material in silos. Nevertheless, many important aspects such as wall pressure, to which silo structures are subjected, still remain uncertain. Numerical simulations based on the finite element method have become a valuable tool to simulate the behavior of granular material in silos at rest and during their flow and to estimate the actions for which the structure has to be designed. However, great differences between various FE software packages have been observed. In this article, the results of two different FE software packages, the general-purpose software ANSYS and a special non-linear dynamic program called SILO, are compared, and the main problems of numerical simulations of granular flow in silos are discussed. Stresses of granular material are calculated during filling and discharge for two- and three-dimensional geometries, including different eccentricities of the outlet. Some numerical problems appear in both models when the bin is filled in several layers. Lateral pressures obtained with both models are similar for filling, but several differences may be observed during discharge. The ANSYS model presents some problems after short simulation discharge time, while the SILO model can simulate almost the entire process of discharge. [ABSTRACT FROM AUTHOR]

PURPOSE: The aim of this study was to assess the influence of age on the functional activity of the multidrug efflux transporter P-glycoprotein (P-gp) at the human blood-brain barrier. METHODS: Seven young (mean age: 27 +/- 4 years) and six elderly (mean age: 69 +/- 9 years) healthy volunteers underwent dynamic (R)-[(11)C]verapamil (VPM) positron emission tomography (PET) scans and arterial blood sampling. Parametric distribution volume (DV) images were generated using Logan linearisation, and age groups were compared with statistical parametric mapping (SPM). Brain regions that SPM analysis had shown to be most affected by age were analysed by a region of interest (ROI)-based approach using a maximum probability brain atlas, before and after partial volume correction (PVC). RESULTS: SPM analysis revealed significant clusters of DV increases in cerebellum, temporal and frontal lobe of elderly compared to younger subjects. In the ROI-based analysis, elderly subjects showed significant DV increases in amygdala (+30%), insula (+26%) and cerebellum (+25%) before PVC, and in insula (+33%) after PVC. CONCLUSIONS: Increased VPM DV values in the brains of elderly subjects suggest a decrease in cerebral P-gp function with increasing age. [ABSTRACT FROM AUTHOR]

The article discusses an analysis of the piezoelectric lithium sulfate monohydrate and its relationship with the static structural properties of the crystal and an external electric field. It indicates the use of X-ray diffraction as the experimental tool in the investigation of the microscopic structure of crystals. It suggests that a topological electron density analysis can characterize the distinctive bond-selective behavior of Li2SO4H2O under an external electric perturbation.

PURPOSE: To report the outcome of a prospective randomized safety and performance trial of 2 access site closure devices versus a wound dressing. METHODS: Between October 2005 and July 2006, 852 consecutive patients (605 men; mean age 67 years) undergoing diagnostic or interventional catheterization procedures thru a 5- or 6-F femoral sheath were randomized to one of the 3 closure methods: a collagen plug device (Angio-Seal), a clip (StarClose), or a wound dressing (D-Stat Dry). The efficacy of the devices was assessed, as well as the complications occurring at the puncture site during the hospital stay. The primary endpoint of the study was the cumulative incidence of access site pseudoaneurysm, major access site bleeding requiring transfusion, access site vascular surgery, or death from all causes. RESULTS: There were no significant differences in baseline characteristics between the 3 treatment groups. The primary endpoint was reached in 20 (7.1%) of 281 patients treated with D-Stat Dry and in 11 (1.9%) of 571 patients treated with the mechanical closure devices (p<0.0001). There was no significant difference among the mechanical closure devices concerning the incidence of the primary endpoint (Angio-Seal 1.1% versus StarClose 2.8%; p = 0.13). CONCLUSION: The collagen plug device had the lowest rates of major and minor access site-related complications after removal of 5- or 6-F femoral sheaths. The difference between the mechanical closure devices concerning the incidence of the primary endpoint did not reach statistical significance. The wound dressing showed significantly higher major and minor complication rates. [ABSTRACT FROM AUTHOR]

Purpose: To determine if angioplasty of atherosclerotic renal artery stenosis, which reduces the activation of the renin-angiotensin-aldosterone system (RAAS), may lead to regression of left ventricular hypertrophy. Methods: The study included 102 patients (58 men; mean age 67 years, range 66-69) who underwent stent-supported percutaneous transluminal renal angioplasty (PTRA) and were included in a clinical follow-up program (mean 24+/-14 months, range 6-60). As a control group, 101 contemporaneous patients (68 men; mean age 68 years, range 66-70) with essential hypertension were investigated. The primary endpoint was the change in left ventricular mass index (LVMI) determined by echocardiography. Results: Mean follow-up intervals were 24+/-14 months (range 6-60) in the study group and 27+/-14 months (range 6-60) in the controls (p = 0.09). LVMI decreased significantly by -10+/-26 g/m(2) in the study group, while it increased significantly by 9+/-28 g/m(2) in the control group (p = 0.001 between groups). In the study group, mean arterial blood pressure was significantly reduced from 99+/-11 mmHg to 90+/-11 mmHg (p<0.0001) during follow-up despite a significant reduction in medication, whereas it increased significantly from 102+/-11 mmHg to 105+/-11 mmHg (p = 0.008) in the control group, although medication was significantly increased. After adjustment for various factors and covariables, PTRA prevailed as an independent predictor for regression of LVMI (p = 0.038). Conclusion: PTRA induces regression of LVMI that is independent of the reduction in blood pressure induced by this procedure. Reduced activity of the RAAS may account for this regression. [ABSTRACT FROM AUTHOR]

Purpose: To report the 12- and 24-month results after directional atherectomy (DA) of below-the-knee (BTK) arterial lesions with the SilverHawk device.Methods: Forty-nine BTK lesions in 36 patients (58% men; mean age 70+/-11 years) with peripheral occlusive disease of the lower limbs were treated with DA; 19 (53%) of the limbs were classified with Rutherford-Becker 4 or 5 ischemia. Target lesions were in the popliteal artery (n = 6, 12%), tibioperoneal trunk (n = 25, 51%), peroneal artery (n = 10, 20%), anterior tibial artery (n = 5, 10%), and posterior tibial artery (n = 3, 6%). Nine (18%) lesions were located in a stent. Twelve lesions extended to 2 artery segments. The average degree of diameter stenosis was 89%+/-10% (range 70%-100%); there were 11 (22%) occlusions. The mean lesion length was 48+/-28 mm.Results: Sixteen (33%) lesions were treated after predilation; 33 (67%) lesions were treated with primary DA. All but 1 (2%) lesion could be treated with DA. In 19 (39%) lesions, additional balloon angioplasty was performed, and 2 (4%) lesions required stent implantation as a result of dissection. The mean stenosis diameter after DA was 12%+/-18% (range 0%-100%). After additional therapy, the mean stenosis diameter was 8%+/-9% (range 0%-100%). A residual stenosis

In this study, we provide a molecular signature of highly enriched CD34+ cells from bone marrow of untreated patients with chronic myelogenous leukemia (CML) in chronic phase in comparison with normal CD34+ cells using microarrays covering 8746 genes. Expression data reflected several BCR-ABL-induced effects in primary CML progenitors, such as transcriptional activation of the classical mitogen-activated protein kinase pathway and the phosphoinositide-3 kinase/AKT pathway as well as downregulation of the proapoptotic gene IRF8. Moreover, novel transcriptional changes in comparison with normal CD34+ cells were identified. These include upregulation of genes involved in the transforming growth factorβ pathway, fetal hemoglobin genes, leptin receptor, sorcin, tissue inhibitor of metalloproteinase 1, the neuroepithelial cell transforming gene 1 and downregulation of selenoprotein P. Additionally, genes associated with early hematopoietic stem cells (HSC) and leukemogenesis such as HoxA9 and MEIS1 were transcriptionally activated. Differential expression of differentiation-associated genes suggested an altered composition of the CD34+ cell population in CML. This was confirmed by subset analyses of chronic phase CML CD34+ cells showing an increase of the proportion of megakaryocyte-erythroid progenitors, whereas the proportion of HSC and granulocyte–macrophage progenitors was decreased in CML. In conclusion, our results give novel insights into the biology of CML and could provide the basis for identification of new therapeutic targets.Leukemia (2007) 21, 494–504. doi:10.1038/sj.leu.2404549; published online 25 January 2007 [ABSTRACT FROM AUTHOR]

Summary:The combination of Cyclosporin A (CSA) and Methotrexate (MTX) is considered to be the standard regimen for the prevention of graft-versus-host disease (GVHD) after stem cell transplantation (SCT) from HLA-identical siblings. Mycophenolate Mofetil (MMF) has been widely used for GVHD prophylaxis after nonmyeloablative SCT, but experience following myeloablative therapy is still limited. We retrospectively compared CSA/MTX and CSA/MMF in 93 patients (median age 35 years, range 17-59 years, male subjects 48, female subjects 45) with acute myeloid leukemia (n=33), myelodysplastic syndrome (MDS) (n=3), acute lymphoblastic leukemia (ALL) (n=20) or chronic myeloid leukemia (n=37) who received CSA/MMF (n=26) or CSA/MTX (n=67) as GVHD prophylaxis following high-dose therapy and allogeneic SCT from HLA-identical siblings. No statistically significant differences were found in overall survival, relapse rate, treatment-related mortality and acute or chronic GVHD. Time to myeloid recovery was significantly shorter in patients who received CSA/MMF. We conclude that the combination of CSA/MMF appears equivalent to CSA/MTX for GVHD prophylaxis in patients receiving conventional-intensity SCT from HLA-identical siblings.Bone Marrow Transplantation (2005) 35, 1089-1093. doi:10.1038/sj.bmt.1704956 Published online 11 April 2005 [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about the use of single-agent thalidomide for treatment of first relapse following high-dose chemotherapy in patients with multiple myeloma.

Summary:Following induction therapy and 4?g/m2 cyclophosphamide, a single dose of 12?mg polyethyleneglycol-conjugated G-CSF (pegfilgrastim; n=12) or daily doses of unconjugated G-CSF (8.5?µg/kg/day) (n=12) were administered to myeloma patients. Pegfilgrastim was associated with an earlier leukocyte recovery (12 vs 14 days) and peripheral blood CD34+cell peak (12 vs 15 days). The peripheral blood CD34+cell peak was lower in the pegfilgrastim group (78 vs 111/µl). Following high-dose melphalan (200?mg/m2) and autografting, leukocyte and platelet reconstitution was similar in both groups and stable blood counts were observed 100 days post transplant. In summary, a single dose of pegfilgrastim after chemotherapy is capable of mobilizing a sufficient number of CD34+cells for successful autografting with early engraftment and sustained hematological reconstitution in patients with myeloma. These data provide the basis for randomized studies evaluating the optimal dose and time of pegfilgrastim as well as long-term outcome in larger cohorts of patients.Bone Marrow Transplantation (2005) 35, 33-36. doi:10.1038/sj.bmt.1704702 Published online 8 November 2004 [ABSTRACT FROM AUTHOR]

Background The aim of this study was to investigate preservation of anti-leukemic activity and protection from opportunistic infections after transplantation of allogeneic CD34 + cells in patients with hematologic malignancies and bad prognosis. Methods Thirty-three patients [median age 42 years, range 23-55 years, diagnosis AML/myelodysplastic syndrome (MDS) 14, ALL nine, CML seven and multiple myeloma (MM) three] received myeloablative conditioning followed by infusion of selected CD34 + cells from matched unrelated donors (31) or HLA-identical siblings (two). Early donor lymphocyte infusions (DLI; 0.5 and 1.0×10 6 CD3 + cells/kg) were given while patients were on immunosuppressive therapy. Results Ninety-seven per cent of patients engrafted and 24 of 29 patients surviving more than 30 days received at least one pre-emptive DLI. Three patients (10%) developed acute (a)GvHD (two grade I-II, one grade III-IV) spontaneously, and 16 patients (67%) developed aGvHD after DLI (12 grade I-II, four grade III-IV). Eight of 24 evaluable patients developed chronic (c)GvHD (33%, six limited, two extensive). After a median follow-up of 590 days (range 138-1610 days) 18 patients were alive (55%), 16 in complete remission (CR), one in hematologic and one in molecular relapse. Seven patients died after relapse (21%) and eight died from transplantation-related causes (24%). Patients with myeloid malignancies had a significantly better survival than patients with ALL or MM (74%±10 vs. 30%±13, P <0.05). Discussion Early pre-emptive low-dose DLI following transplantation of selected CD34 + cells from unrelated donors after myeloablative conditioning is feasible and effective without undue toxicity, especially in patients with myeloid malignancies. [ABSTRACT FROM AUTHOR]